crossing96/oncoscreening huggingface dataset:
Association Between Use of Antithrombotic Medication and Hematuria-Related Complications.	IMPORTANCE: Antithrombotic medications are among the most commonly prescribed medications. OBJECTIVE: To characterize rates of hematuria-related complications among patients taking antithrombotic medications. DESIGN, SETTING, AND PARTICIPANTS: Population-based, retrospective cohort study including all citizens in Ontario, Canada, aged 66 years and older between 2002 and 2014. The final follow-up date was December 31, 2014. EXPOSURES: Receipt of an oral anticoagulant or antiplatelet medication. MAIN OUTCOMES AND MEASURES: Hematuria-related complications, defined as emergency department visit, hospitalization, or a urologic procedure to investigate or manage gross hematuria. RESULTS: Among 2 518 064 patients, 808 897 (mean [SD] age, 72.1 [6.8] years; 428 531 [53%] women) received at least 1 prescription for an antithrombotic agent over the study period. Over a median follow-up of 7.3 years, the rates of hematuria-related complications were 123.95 events per 1000 person-years among patients actively exposed to antithrombotic agents vs 80.17 events per 1000 person-years among patients not exposed to these drugs (difference, 43.8; 95% CI, 43.0-44.6; P < .001, and incidence rate ratio [IRR], 1.44; 95% CI, 1.42-1.46). The rates of complications among exposed vs unexposed patients (80.17 events/1000 person-years) were 105.78 for urologic procedures (difference, 33.5; 95% CI, 32.8-34.3; P < .001, and IRR, 1.37; 95% CI, 1.36-1.39), 11.12 for hospitalizations (difference, 5.7; 95% CI, 5.5-5.9; P < .001, and IRR, 2.03; 95% CI, 2.00-2.06), and 7.05 for emergency department visits (difference, 4.5; 95% CI, 4.3-4.7; P < .001, and IRR, 2.80; 95% CI, 2.74-2.86). Compared with patients who were unexposed to thrombotic agents, the rates of hematuria-related complications were 191.61 events per 1000 person-years (difference, 117.3; 95% CI, 112.8-121.8) for those exposed to both an anticoagulant and antiplatelet agent (IRR, 10.48; 95% CI, 8.16-13.45), 140.92 (difference, 57.7; 95% CI, 56.9-58.4) for those exposed to anticoagulants (IRR, 1.55; 95% CI, 1.52-1.59), and 110.72 (difference, 26.5; 95% CI, 25.9-27.0) for those exposed to antiplatelet agents (IRR, 1.31; 95% CI, 1.29-1.33). Patients exposed to antithrombotic agents, compared with patients not exposed to these drugs, were more likely to be diagnosed as having bladder cancer within 6 months (0.70% vs 0.38%; odds ratio, 1.85; 95% CI, 1.79-1.92). CONCLUSIONS AND RELEVANCE: Among older adults in Ontario, Canada, use of antithrombotic medications, compared with nonuse of these medications, was significantly associated with higher rates of hematuria-related complications (including emergency department visits, hospitalizations, and urologic procedures to manage gross hematuria).	bladder
Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.	BACKGROUND: Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets. METHODS: Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models. RESULTS: In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial-mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with β-catenin, Twist and Snail expression, but negatively with E-cadherin expression. CONCLUSIONS: This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.	bladder
Photochemical internalization in bladder cancer - development of an orthotopic in vivo model.	The possibility of using photochemical internalization (PCI) to enhance the effects of the cytotoxic drug bleomycin is investigated, together with photophysical determination and outlines of a possible treatment for intravesical therapy of bladder cancer. In vitro experiments indicated that the employment of PCI technology using the novel photosensitizer TPCS(2a)® can enhance the cytotoxic effect of bleomycin in bladder cancer cells. Furthermore, experiments in an orthotopic in vivo bladder cancer model show an effective reduction in both the necrotic area and the bladder weight after TPCS(2a) based photodynamic therapy (PDT). The tumor selectivity and PDT effects may be sufficient to destroy tumors without damaging the detrusor muscle layer. Our results present a possible new treatment strategy for non-muscle invasive bladder cancer, with the intravesical instillation of the photosensitizer and bleomycin followed by illumination through an optic fiber by using a catheter.	bladder
Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer.	BACKGROUND/AIMS: Tetrandrine and Fangchinoline (Fcn) are two natural products that are found in Stephania tetrandra. Tetrandrine is a known anti-bladder cancer compound, but the effects of Fcn on bladder cancer have been previously unclear. In the present study, we focused on the anti-tumor effects of Fcn on bladder cancer. METHODS AND RESULTS: We treated T24 and 5637 bladder cancer cell lines with Fcn in vitro. We observed that Fcn inhibited the viability of bladder cancer cells in a concentration-dependent manner. The expression of PCNA, a biomarker of proliferation, was down-regulated. Fcn treatment induced both apoptosis and autophagy in bladder cancer cells, as shown by the increased cleavage of caspase-3, an up-regulated LC3-II/LC3-I ratio and the down-regulated p62 level. Blocking autophagy with 3-MA (3-Methyladenine) enhanced Fcn-induced apoptosis, indicating that Fcn-induced autophagy was adaptive. Additionally, we observed that Fcn treatment inhibited mTOR and reduced the intracellular ATP levels. The exogenous addition of methyl pyruvate (MP) to compensate metabolic substrates alleviated Fcn-induced apoptosis and autophagy. CONCLUSIONS: Our data indicated that Fcn caused an impairment in energy generation, which led to apoptosis and adaptive autophagy in bladder cancer. These results demonstrated that Fcn may be a potential candidate for use in the prevention and treatment of bladder cancer.	bladder
CK20 and p53 Immunohistochemical Staining Patterns in Urinary Bladder Specimens With Equivocal Atypia.	CONTEXT: - Urinary bladder flat carcinoma in situ (CIS) is a worrisome lesion, requiring aggressive surveillance and treatment. Cytokeratin 20 (CK20) and p53 are common immunohistochemical antibodies used to supplement CIS diagnosis in biopsy samples. However, existing data come primarily from unequivocally benign and malignant specimens. OBJECTIVE: - To correlate these markers in specimens with borderline histology with outcomes. DESIGN: - CK20 and p53 immunohistochemistry was analyzed for staining pattern, classified as CIS pattern (both stains yielding strong labeling of the area of concern), discordant (only 1 stain yielding CIS pattern), indeterminate (1 or both stains yielding partial or equivocal labeling), or benign (both stains yielding a benign pattern). RESULTS: - Specimens with equivocal atypia (n = 69) from 65 patients were studied. There were 9 specimens (13%) that had a CIS staining pattern, 18 (26%) were discordant, 31 (45%) were indeterminate, and 11 (16%) were benign. Of the discordant specimens, 13 labeled for CK20 but not p53, whereas 5 showed the opposite. Most specimens (n = 47; 68%) were obtained from patients with a known history of bladder cancer, of which recurrence developed in 27, with an average interval of 37 months (range, 2-216 months). A subset (n = 22; 34%) had no prior history of bladder cancer, from which only 1 patient with CK20-positive/p53-equivocal staining later developed diagnostic carcinoma. CONCLUSIONS: - In our cohort of specimens with equivocal urothelial atypia, very few patients without a prior diagnosis of bladder cancer progressed to diagnostic cancer (1 of 22), suggesting that staining results should be interpreted with caution in de novo atypia. Patients with a known history of bladder cancer had a substantial rate of recurrence, independent of staining pattern.	bladder
Monitoring Treatment Response and Metastatic Relapse in Advanced Bladder Cancer by Liquid Biopsy Analysis.	Of the patients undergoing radical cystectomy, 20-80% experience relapse. Minimally invasive methods for early detection of metastatic relapse after cystectomy and for monitoring ongoing therapy are urgently needed to improve individualised follow-up and treatment. Therefore, we evaluated the use of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84 personalised digital droplet polymerase chain reaction assays targeting 61 genes. Patients were prospectively recruited between 2013 and 2017. Patients with metastatic relapse had significantly higher ctDNA levels compared with disease-free patients (p<0.001). The median positive lead time between ctDNA detection in plasma and diagnosis of relapse was 101 d after cystectomy (range 0-932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions. PATIENT SUMMARY: Measurement of tumour-specific mutations in plasma and urine may be a powerful tool to monitor response during treatment and identify early signs of metastatic disease.	bladder
Computer-assisted cystoscopy diagnosis of bladder cancer.	OBJECTIVES: One of the most reliable methods for diagnosing bladder cancer is cystoscopy. Depending on the findings, this may be followed by a referral to a more experienced urologist or a biopsy and histological analysis of suspicious lesion. In this work, we explore whether computer-assisted triage of cystoscopy findings can identify low-risk lesions and reduce the number of referrals or biopsies, associated complications, and costs, although reducing subjectivity of the procedure and indicating when the risk of a lesion being malignant is minimal. MATERIALS AND METHODS: Cystoscopy images taken during routine clinical patient evaluation and supported by biopsy were interpreted by an expert clinician. They were further subjected to an automated image analysis developed to best capture cancer characteristics. The images were transformed and divided into segments, using a specialised color segmentation system. After the selection of a set of highly informative features, the segments were separated into 4 classes: healthy, veins, inflammation, and cancerous. The images were then classified as healthy and diseased, using a linear discriminant, the naïve Bayes, and the quadratic linear classifiers. Performance of the classifiers was measured by using receiver operation characteristic curves. RESULTS: The classification system developed here, with the quadratic classifier, yielded 50% false-positive rate and zero false-negative rate, which means, that no malignant lesions would be missed by this classifier. CONCLUSIONS: Based on criteria used for assessment of cystoscopy images by medical specialists and features that human visual system is less sensitive to, we developed a computer program that carries out automated analysis of cystoscopy images. Our program could be used as a triage to identify patients who do not require referral or further testing.	bladder
Impact of Packed Red Blood Cells and Fresh Frozen Plasma Given During Radical Cystectomy and Urinary Diversion on Cancer-related Outcome and Survival: An Observational Cohort Study.	BACKGROUND: The relationship between blood transfusion and cancer-related outcome and mortality is controversial. OBJECTIVE: To assess if perioperative administration of packed red blood cell (PRBC) and fresh frozen plasma (FFP) units affects disease progression and survival after radical cystectomy for bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: We conducted an observational single-centre cohort study of a consecutive series of 885 bladder cancer patients, between 2000 and 2015. Perioperative blood transfusion was defined as need for PRBCs and FFP transfusion within the first 24h after the beginning of surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Disease recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique and log-rank test. RESULTS AND LIMITATIONS: A total of 267/885 patients (23%) were transfused; 187/267 patients (70%) received only PRBCs (median 2 units [interquartile range: 1-2]) and 80/267 patients (30%) received PRBCs (2 [2-3]) plus FFP (2 [2-2]). Receipt of PRBCs or PRBCs+FFP was associated with a higher 90 d mortality (7.0% vs 7.5% vs 2.9%; p=0.016), inferior 5 yr recurrence-free survival (no transfusion 92%, PRBCs 74%, p=0.005; PRBCs+FFP 49%, p=0.002), 5 yr cancer-specific survival (no transfusion 74%, PRBCs 60%, PRBCs+FFP 49%, all p<0.001), and 5 yr overall survival (no transfusion 90%, PRBCs 70%, PRBCs+FFP 34%, all p<0.001). In multivariate analysis, blood transfusion was predictive for all-cause mortality (PRBCs [hazard ratio; HR 1.610; p<0.001] and PRBCs+FFP [HR 1.640; p=0.003]) and cancer-specific mortality (PRBCs [HR 1.467; p=0.010] and PRBCs+FFP [HR 1.901; p=0.021]). Limitations include selection bias and lack of standardised transfusion criteria. CONCLUSIONS: Administration of PRBCs and FFP was associated with significantly inferior cancer-specific and overall survival. Relevant preoperative factors for receiving blood transfusion were neoadjuvant chemotherapy, preoperative anaemia, older age, and American Society of Anesthesiologists score ≥3, and these factors emphasise the importance of preoperative optimisation of patients undergoing cystectomy. PATIENT SUMMARY: Blood transfusion during radical cystectomy was associated with inferior survival.	bladder
Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors.	AIMS: Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored. MAIN METHODS: The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT). KEY FINDINGS: DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity. SIGNIFICANCE: Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior.	bladder
Long non-coding RNA HULC promotes bladder cancer cells proliferation but inhibits apoptosis via regulation of ZIC2 and PI3K/AKT signaling pathway.	BACKGROUND: Bladder cancer is the fourth most common malignancy among men urinary system and it is a complex disease caused by genetic and environmental factors. OBJECTIVE: This study aimed to evaluate the effects of hepatocellular carcinoma up-regulated long non-coding RNA (lncRNA HULC) on bladder cancer and to reveal the potential mechanisms. METHODS: The expression level of HULC in 276 bladder cancer patients was detected. The association of HULC level with patient recurrence was performed by Kaplan-Meier and log-rank test. Moreover, T24 and RT4 cells were transfected with HULC and ZIC2 targeted siRNAs, HULC expressing vector and corresponding controls. Subsequently, cell viability, apoptosis and tumorigenesis were examined. RESULTS: The expression level of HULC was increased in bladder cancer tissues. High expression of HULC was correlated with advanced clinical stage and lower recurrence-free rate. HULC was remarkably promoted cell viability but inhibited apoptosis, meanwhile conspicuously increased the expression of Cyclin A/D1/E and Bcl-2. Xenograft tumor model showed that HULC promoted tumor weights in vivo. CONCLUSIONS: LncRNA HULC promoted bladder cancer cells proliferation and inhibited apoptosis.	bladder
Primary Urinary Bladder Osteosarcoma in a Dog.	A 13-year-old, female Welsh corgi had a clinical history of haematuria and cystitis for 2-3 months. A 4 × 3 × 2 cm mass was excised surgically from the apex of the urinary bladder. A primary urinary bladder osteosarcoma was diagnosed histologically. Primary urinary bladder osteosarcoma is a rare tumour in man and animals. To the author's knowledge, there is no previously published report of a primary canine urinary bladder osteosarcoma.	bladder
Personalized peptide vaccination as second-line treatment for metastatic upper tract urothelial carcinoma.	This study investigated the applicability of personalized peptide vaccination (PPV) for patients with metastatic upper tract urothelial cancer (mUTUC) after failure of platinum-based chemotherapy. In this single arm, open-label, phase II clinical trial, patients with mUTUC received PPV at a single institution. Personalized peptide vaccination treatment used a maximum of four peptides chosen from 27 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for six s.c. injections weekly as one cycle. The safety of PPV, as well as its influence on host immunity and effect on overall survival were assessed. Forty-eight patients were enrolled in this study. Personalized peptide vaccinations were well tolerated without severe adverse events. Median survival time was 7.3 months (95% confidence interval [CI], 5.3-13.1) with 13.0 months for patients receiving combined salvage chemotherapy (95% CI, 5.7-17.5) and 4.5 months for patients receiving PPV alone (95% CI, 1.7-10.1) (P = 0.080). Patients with positive CTL responses showed a significantly longer survival than patients with negative CTL responses (hazard ratio, 0.37; 95% CI, 0.16-0.85; P = 0.019). Multivariate Cox regression analysis showed that lower numbers of Bellmunt risk factors and lower levels of B-cell activating factor were significantly associated with favorable overall survival for patients under PPV treatment. This study indicated that PPV for patients with mUTUC after failure of platinum-based chemotherapy induced substantial peptide-specific CTL responses without severe adverse events and has the potential to prolong survival when combined with salvage chemotherapy. UMIN Clinical Trials Registry ID: 000001854.	bladder
Association between long-term low-intensity cigarette smoking and incidence of smoking-related cancer in the national institutes of health-AARP cohort.	An increasing proportion of US smokers smoke ≤10 cigarettes per day (CPD) or do not smoke every day, yet the health effects of low-intensity smoking are poorly understood. We identified lifelong smokers of <1 or 1-10 CPD and evaluated risk of incident cancer among 238,525 cancer-free adults, aged 59-82, in the NIH-AARP Diet and Health Study. A questionnaire administered in 2004-2005 assessed CPD during nine age-periods (<15 to ≥70). We estimated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable-adjusted Cox proportional hazards regression with age as the underlying time metric. Of the 18,233 current smokers, (7.6%), 137 and 1,243 reported consistently smoking <1 CPD and 1-10 CPD, respectively. Relative to never smokers, current smokers who reported consistently smoking 1-10 CPD over their lifetime were 2.34 (95% CI = 1.86-2.93) times more likely to develop smoking-related cancer. Current lifetime smokers of <1 CPD were 1.89 (95% CI = 0.90-3.96) times more likely to develop tobacco-related cancer, although the association did not reach statistical significance. Associations were observed for lifelong smoking of ≤10 CPD with lung cancer (HR = 9.65, 95% CI = 6.93-13.43); bladder cancer (HR = 2.22, 95% CI = 1.22-4.05); and pancreatic cancer (HR = 2.03, 95%CI: 1.05-3.95). Among lifelong ≤10 CPD smokers, former smokers had lower risks of smoking-related cancer with longer time since cessation and longer smoking duration. Lifelong <1 and 1-10 CPD smokers are at increased risk of incident cancer relative to never smokers and would benefit from cessation, providing further evidence that even low-levels of cigarette smoking cause cancer.	bladder
A low psoas muscle volume correlates with a longer hospitalization after radical cystectomy.	BACKGROUND: Recently, sarcopenia has been reported as a new predictor for patient outcomes or likelihood of post-operative complications. The purpose of this study was to evaluate the association of the psoas muscle volume with the length of hospitalization among patients undergoing radical cystectomy. METHODS: A total of 63 (80.8%) male patients and 15 (19.2%) female patients who underwent radical cystectomy for their bladder cancer in our institution from 2000 to 2015 were analyzed. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area calculated using axial computed tomography at the level of the umbilicus (cm(2)) by the square of the body height (m(2)). Longer hospitalization was defined as hospitalization exceeding 30 days after surgery. RESULTS: The median PMIs (mean ± standard deviation) were 391 (394 ± 92.1) and 271 (278 ± 92.6) cm(2)/m(2) in men and women, respectively. Thus, the PMIs of male patients were significantly larger than those of females (p < 0.001). Based on the differences in gender, we analyzed 63 male patients for a further analysis. In male patients, those hospitalized longer showed a significantly smaller PMI than those normally discharged (377 ± 93.1 vs. 425 ± 83.4; p = 0.04). Similarly, male patients with a small PMI (<400) had a significantly worse overall survival (p = 0.02) than those with a large PMI (≥400). CONCLUSIONS: The presence of sarcopenia was found to be associated with significantly longer hospitalization after radical cystectomy in male patients. Furthermore, in men, a PMI <400 may suggest a significantly worse prognosis.	bladder